The present invention relates generally to vaccine compositions and methods of making and using the same. More specifically, the invention pertains to a Mycoplasma bacterin demonstrating improved efficacy in protecting cattle from mortality and morbidity associated with Bovine Respiratory Disease complex.
Initially called pleuropneumonia-like-organisms (PPLO) because of their similarity to the pleuropneumonia agent of cattle, members of the genus Mycoplasma are opportunistic invaders that cause severe mortality and morbidity in cattle of all ages. Mycoplasma infection has been associated with a variety of bovine diseases including keratoconjunctivitis, mastitis, pneumonia, synovitis, and have been implicated in otitis, abortion and low fertility, and chronic respiratory disease (O""Berry et al, 1966, Jasper, 1982 and Alexander et al, 1985).
The most prevalent and pathogenic species of Mycoplasma isolated from cattle is M. bovis, responsible for more than half of the reported isolates in dairy cattle (L. Judge, 1997). Recently, M. bovis was identified as a common pathogen in young dairy calves ranging from 14 to approximately 100 days of age. Other strains of Mycoplasma frequently identified as a significant cause of morbidity in cattle include M. alkalescens and M. bovirhinis. 
One of the most important diseases affecting cattle is bovine respiratory disease complex (BRD), which has a huge economic impact worldwide on cattle production. BRD may affect cows and calves but occurs most frequently in younger animals. Although the disease complex involves many different components, including environmental factors, host factors, viruses, bacteria and other infectious agents, Mycoplasma has increasingly been implicated as a cause. Affected cattle show respiratory signs such as fever, depression, anorexia, difficulty breathing, nasal and ocular discharge, coughing, sneezing, gasping, grunting, recumbence and death. Animals may stand with their elbows abducted and their necks extended in an attempt to breath.
Diagnosis of BRD is based on clinical signs with a definitive diagnosis established via culture isolation. However, Mycoplasma can be difficult to culture because its isolation requires reduced oxygen conditions, special culture media, and long culture periods for growth. Complicating treatment of the disease complex is that Mycoplasma are resistant to conventional antibiotic therapy because the organisms lack a cell wall (Razin et al, 1998).
Because no effective antimicrobial therapy exists to treat Mycoplasma infection, prevention relies on instituting effective husbandry measures for control, including providing proper ventilation, reducing the presence of dust and debris, reducing stress, preventing overcrowding, and instituting good animal husbandry procedures including quarantine of new arrivals to prevent the introduction of a Mycoplasma-infected animal into a herd. However, whether quarantine practices will prevent a Mycoplasma-associated outbreak is questionable since the organisms are often found as commensals in the respiratory tract of apparently normal cattle. It has been suggested that Mycoplasma mastitis may result from the transfer of the organism from the lungs to the mammary gland by hematogenous or other routes (Jasper, 1982). Indeed, respiratory outbreaks followed by cases of mastitis that are also antibiotic-resistant have been reported (Gonzalaz, 1992).
M. bovis may be asymptomatically present as commensal organisms in the upper respiratory tracts of older animals, where the organisms form a constant source of infection for young animals that are more susceptible to developing clinical disease (Brank et al., 1999). Calves may also be exposed to Mycoplasma infection during calving by contact with the urogenital tract, where Mycoplasma may be shed in the vaginal discharge of heifers. Organisms may also be present in nasal discharges and milk of shedding animals. The prepuce and distal urethra have been found to be colonized by Mycoplasma in the genital tract of apparently normal bulls, resulting in the production of infected semen and may be a path for the dissemination of infection (Jasper et al, 1974).
Vaccination is widely employed as a means to control the morbidity and mortality associated with infectious agents. Generally, vaccines are designed to stimulate a protective immune response in the recipient such that subsequent exposure to the particular infectious agent does not result in disease. Almost all of the vaccines used today to provide immunity against viral or bacterial infections fall into three main categories: 1) live, attenuated organisms, 2) inactivated whole organisms, or 3) subunit vaccines. In all situations, the goal is to present antigens to the recipient""s immune system sufficient to produce a protective response without giving the recipient the disease.
Although Mycoplasma infection remains a significant cause of morbidity and mortality for cattle growers, vaccination as a method of preventing Mycoplasma infection is not widely employed. Commercial vaccines with proven efficacy against bovine Mycoplasma species are not readily available and autogenous vaccines have shown little to modest success. Autogenous vaccines are produced from specific samples or isolates of organisms obtained from diseased animals. The products are typically produced by diagnostic laboratories, university diagnostic facilities or commercial suppliers (for example, American Animal Health, Inc., Fort Worth, Tex.). The use of autogenous vaccines to control bovine Mycoplasma infection has been disappointing. Because M. bovis exhibits multiple distinct antigens even within a strain, immunization with one strain of Mycoplasma provides little or no cross protection against other strains.
Because of this deficiency and others inherent in the prior art, it would be advantageous to provide a vaccine that induces protection in cattle against Mycoplasma infection, especially one useful in reducing mortality and morbidity associated with BRD.
Briefly described, the present invention relates to a novel vaccine capable of inducing a protective response in cattle against Mycoplasma infection, especially infection associated with BRD. Further provided is a method of producing the vaccine. Finally, the present invention also provides a method of immunizing a calf or cow against Mycoplasma infection, especially Mycoplasma-associated BRD, comprising administering to the calf or cow a dose of a vaccine made according to the present invention in an amount effective to induce a protective response in the animal.
In one embodiment of the present invention, the vaccine is a whole-cell, inactivated bacterin comprising at least two strains of Mycoplasma bovis, an adjuvant and a pharmaceutically acceptable carrier.
In an alternate embodiment, the bacterin of the present invention comprises at least one strain of Mycoplasma bovis and, in addition, at least one Mycoplasma isolate of a species other than M. bovis. For example, an isolate of M. alkalescens or M. bovirhinis may be added to the M. bovis bacterin.
In yet another embodiment, the present invention provides a synergistic combination vaccine comprising at least one viral, bacterial, fungal or parasitic bovine antigen or antiserum capable of inducing a protective response against a bovine pathogen other than Mycoplasma and, in addition, at least one strain of Mycoplasma bovis and at least one strain of a Mycoplasma species other than M. bovis. For example, an inactivated or attenuated strain of Pasteurella, Haemophilus or Clostridium may be added to a Mycoplasma bacterin to provide a combination vaccine within the scope of the present invention.
Also provided is a process for the production of a multivalent Mycoplasma bacterin of the present invention. In one embodiment, the vaccine production process comprises culturing at least two Mycoplasma strains; harvesting the cultures; inactivating the cultures to produce a bacterin; adjuvanting the bacterin; and dispensing the bacterin in sterile containers.
The present invention further provides a method for producing a protective immune response in cattle against Mycoplasma infection, especially infection associated with bovine respiratory disease (BRD). In one embodiment, the method for inducing immunity comprises administering to a cow or calf a dose of a Mycoplasma bacterin made according to the present invention in an amount sufficient to protect the animal from BRD.